1. Field of the Invention
The invention relates to a reaction vessel for producing a sample, in particular a crystal, from a substance in solution or in liquid form, having several reaction chambers, each of which forms a separate gas chamber, formed by at least one housing part and each reaction chamber has a reservoir and, connected to the reservoir, several reaction areas co-operating therewith to produce a gas exchange.
The invention also relates to a reaction vessel having at least a vessel bottom part with a vessel floor and vessel walls forming at least one reaction chamber, the reaction chamber having a reservoir for liquid agents and at least a reaction area separated from the reservoir and having a gas connection thereto.
The invention further relates to a vessel cover for producing a sample, in particular a crystal, from a substance in liquid form or in solution, having several reaction areas on an underside.
2. The Prior Art X-ray diffraction is one of the most important tools in investigating structures of chemical substances. Particularly in modern molecular biology, crystallographic tests on macro-molecules such as protein and nucleic acids and their numerous complexes can lead to valuable conclusions about their properties and the way in which they work.
The most important aspect of carrying out structural analyses by X-ray diffraction is to be able to produce sufficiently large crystals, particularly single crystals of the substance to be investigated, which are as far as possible fault-free. In the case of biological macro-molecules, because crystal growth is very sensitive and highly dependent on a number of physical and chemical parameters, crystal culture is a factor which severely limits structural investigation in modern biology.
One of the most important methods of producing crystals of macro-molecules is based on the principle of vapour diffusion. This involves mixing a small quantity of the macro-molecule sample with a crystallisation solution and enclosing this solution, in a container, in the form of a droplet with a significantly larger quantity of the crystallisation solution, which is contained separately. By being able to exchange vapour between the crystallisation droplet and the reservoir, a change in concentration is brought about in the crystallisation droplet, which over-saturates the dissolved macro-molecules so that a crystal gradually starts to form in the droplet.
Because growing crystals of macro-molecules is very sensitive and dependent on a whole range of parameters, it is necessary to conduct a lot of tests in order to establish the parameters under which crystals suitable for structural analysis can be grown.
Various systems have been proposed as a means of conducting tests in large numbers, with the most varied combinations of variables influencing crystallisation. A device is known from U.S. Pat. No. 6,039,804 A, for example, which has 24 reservoirs for the crystallisation solvent, every reservoir having four droplet chambers disposed around it. With the droplet chambers disposed in this arrangement and with the arrangements proposed in other solutions, however, only a very small percentage of the surface area available on the device for accommodating droplet chambers is used. With the known systems, however, experience has shown that the process chambers for droplets in the form of what are known as suspended droplets placed on the underside of a chamber cover is fraught with difficulties and prone to error. A glass plate is generally used as a chamber cover. However, it is not always possible to position droplets on a glass plate with sufficient accuracy, which makes optical control of the crystal growth more difficult. Furthermore, because the glass plate is usually placed on the droplet chambers with a sealing layer of silicon grease in between and the silicon grease reduces friction, it frequently happens that the glass plate is inadvertently displaced.
The requirements of modern biology in particular are such that it is necessary to be able conduct an extremely large number of crystallisation tests with the most varied of parameters simultaneously. At the same time, it is also necessary to be able to automate these tests, both in terms of preparation and the controls applied to crystal growth by microscopic observation during the relatively long crystallisation process.